J H Levy1, K T Moore2, M D Neal3, D Schneider4,5, V S Marcsisin2, J Ariyawansa2, J I Weitz5. 1. Department of Anesthesiology and Critical Care, Duke University Medical Center, Durham, NC, USA. 2. Janssen Pharmaceuticals, Janssen Scientific Affairs, Titusville, NJ, USA. 3. Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA. 4. Cardiovascular Research Institute, Department of Medicine, University of Vermont, Burlington, VT, USA. 5. McMaster University and Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada.
Abstract
Essentials Specific reversal agents for managing severe factor Xa inhibitor-associated bleeding are lacking. We assessed 4-factor-prothrombin complex concentrate (4F-PCC) and tranexamic acid (TXA). 4F-PCC, but not TXA, reduced the prothrombin time and increased endogenous thrombin potential. These agents may be viable options for reversal of therapeutic doses of rivaroxaban. SUMMARY: Background Oral activated factor X inhibitors such as rivaroxaban are widely used, but specific reversal agents are lacking. Although four-factor prothrombin complex concentrate (4F-PCC) and tranexamic acid (TXA) are sometimes used to manage serious bleeding, their efficacy is unknown. Prior studies in healthy subjects takingrivaroxaban revealed that 4F-PCC partially reverses the prolonged prothrombin time (PT), and fully restores the endogenous thrombin potential (ETP). The effect of TXA has not been evaluated. Methods In this double-blind, parallel-group study, 147 healthy volunteers givenrivaroxaban 20 mg twice daily for 3 days were randomized after their morning dose on day 4 to receive intravenous 4F-PCC (50 IU kg-1 ), TXA (1.0 g), or saline. Standardized punch biopsies were performed at baseline and after 4F-PCC, TXA or saline administration. Reversal was assessed by measuring bleeding duration and bleeding volume at biopsy sites, and by determining the PT and ETP. Results As compared with saline, 4F-PCC partially reversed the PT and completely reversed the ETP, whereas TXA had no effect. Neither 4F-PCC nor TXA reduced bleeding duration or volume. All treatments were well tolerated, with no recorded adverse events. Conclusions Although 4F-PCC reduced the PT and increased the ETP in volunteers given supratherapeutic doses of rivaroxaban, neither 4F-PCC nor TXA influenced punch biopsy bleeding.
RCT Entities:
Essentials Specific reversal agents for managing severe factor Xa inhibitor-associated bleeding are lacking. We assessed 4-factor-prothrombin complex concentrate (4F-PCC) and tranexamic acid (TXA). 4F-PCC, but not TXA, reduced the prothrombin time and increased endogenous thrombin potential. These agents may be viable options for reversal of therapeutic doses of rivaroxaban. SUMMARY: Background Oral activated factor X inhibitors such as rivaroxaban are widely used, but specific reversal agents are lacking. Although four-factor prothrombin complex concentrate (4F-PCC) and tranexamic acid (TXA) are sometimes used to manage serious bleeding, their efficacy is unknown. Prior studies in healthy subjects taking rivaroxaban revealed that 4F-PCC partially reverses the prolonged prothrombin time (PT), and fully restores the endogenous thrombin potential (ETP). The effect of TXA has not been evaluated. Methods In this double-blind, parallel-group study, 147 healthy volunteers given rivaroxaban 20 mg twice daily for 3 days were randomized after their morning dose on day 4 to receive intravenous 4F-PCC (50 IU kg-1 ), TXA (1.0 g), or saline. Standardized punch biopsies were performed at baseline and after 4F-PCC, TXA or saline administration. Reversal was assessed by measuring bleeding duration and bleeding volume at biopsy sites, and by determining the PT and ETP. Results As compared with saline, 4F-PCC partially reversed the PT and completely reversed the ETP, whereas TXA had no effect. Neither 4F-PCC nor TXA reduced bleeding duration or volume. All treatments were well tolerated, with no recorded adverse events. Conclusions Although 4F-PCC reduced the PT and increased the ETP in volunteers given supratherapeutic doses of rivaroxaban, neither 4F-PCC nor TXA influenced punch biopsy bleeding.
Authors: Christopher W Baugh; Michael Levine; David Cornutt; Jason W Wilson; Richard Kwun; Charles E Mahan; Charles V Pollack; Evie G Marcolini; Truman J Milling; W Frank Peacock; Rachel P Rosovsky; Fred Wu; Ravi Sarode; Alex C Spyropoulos; Todd C Villines; Timothy D Woods; John McManus; James Williams Journal: Ann Emerg Med Date: 2019-11-13 Impact factor: 5.721
Authors: Herm Jan M Brinkman; Frauke Swieringa; Marleen Zuurveld; Alicia Veninga; Sanne L N Brouns; Johan W M Heemskerk; Joost C M Meijers Journal: Res Pract Thromb Haemost Date: 2022-04-25
Authors: Genmin Lu; Polly Pine; Janet M Leeds; Francis DeGuzman; Pratikhya Pratikhya; Joyce Lin; John Malinowski; Stanley J Hollenbach; John T Curnutte; Pamela B Conley Journal: PLoS One Date: 2018-03-28 Impact factor: 3.240